Abstract Number: PB1119
Meeting: ISTH 2020 Congress
Background: Prothrombin Complex Concentrate (PCC) is considered the standard of care for patients on apixaban and rivaroxaban requiring reversal in life-threatening or uncontrolled bleeding. Andexanet alfa (short: andexanet) has recently been approved by the FDA and EMA for this indication.
Aims: To systematically compare the efficacy and safety of andexanet and PCC for reversal of factor Xa-inhibitors in patients presenting with major bleeding.
Methods: A systematic literature search was conducted using Pubmed up to December 2019. Studies with patients on rivaroxaban or apixaban who needed urgent reversal with an antidote for a major bleed were included.
Outcome parameters were haemostatic efficacy and thromboembolic event rate as assessed in each study. The quality of the studies was scored by the MINORS and RoBANS methodologies.
Results: Of 360 citations identified, 7 studies were included. PCC was evaluated in 6 studies and andexanet in one study. All studies had an observational design and no comparative studies were found. Two PCC studies were graded as good quality with a low risk of bias, the andexanet study was graded as moderate with a high risk of bias. Different haemostatic efficacy assessment methods were used across the studies.
|Citation||Antidote||Design||No. patients treated with fXa-inhibitor||Quality (Minors)||Risk of bias (RoBans)||Haemostatic efficacy (%)||Mortality (%)||Thromboembolic events (%)|
|Connolly et al. 2019||Andexanet||Retrospective observational||352 for safety analysis; 254 for efficacy analysis||Moderate||High||81.9 ||13.9||9.7|
|Arachchillage et al. 2019||PCC||Retrospective observational||80||Moderate||Moderate||73.4 ||33.0||3.8|
|Smith et al. 2019||PCC||Retrospective observational||31||Moderate||Moderate||80.6 ||16.1||0|
|Majeed et al. 2017||PCC||Retrospective observational||84||Good||Low||69.1 ||32.0||2.4|
|Sheikh-Taha et al. 2019||PCC||Retrospective observational||29||Moderate||Moderate||72.4 ||27.6||3.4|
|Testa et al. 2018||PCC||Retrospective observational||85||Good||High||81.5 ||17.6||unknown|
|Schulman et al. 2018||PCC||Retrospective observational||66||Good||Low||84.8 ||13.6||7.6|
[Table 1: Results Criteria as defined by ISTH (Khorsand 2016); criteria by Sarode et al. (2013);  no standard criteria]
Haemostasis was achieved in 69-85% of the PCC treated patients and in 82% of the andexanet treated patients. Thromboembolic events occurred in 10% of andexanet treated patients and 0-7.6% in the PCC studies. Overall mortality showed great heterogeneity in the reviewed publications.
Conclusions: In this systemic review PCC and andexanet showed a comparable efficacy profile in patients on factor Xa-inhibitors presenting with major bleeding. Thromboembolic complications differed, probably as a result of patient selection. Due to methodological shortcomings in all studies, more high quality research, including a comparative study of andexanet in relation to PCC, is urgently needed.
To cite this abstract in AMA style:Jaspers TCC, Shudofsky KN, Huisman MV, Meijer K, Khorsand N. Andexanet and Prothrombin Complex Concentrate Give Comparable Haemostatic Efficacy for Major Bleeding in Patients on Factor Xa Inhibitors [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/andexanet-and-prothrombin-complex-concentrate-give-comparable-haemostatic-efficacy-for-major-bleeding-in-patients-on-factor-xa-inhibitors/. Accessed January 28, 2022.
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